Despite improvements in breast cancer diagnosis and treatment, Black women with breast cancer continue to have a worse prognosis than White women. The purpose of this study is to determine whether differences in insulin resistance can explain in part the disparities in breast cancer survival between Black and White women. Insulin resistance is an important component of obesity, the metabolic syndrome and early stage type 2 diabetes, conditions associated with more aggressive breast cancer subtypes and increased mortality. Higher insulin levels in White women have also been associated with increased breast cancer mortality, although this has not been studied in Black women. Given that obesity and diabetes epidemics disproportionately affect minority populations, it is important understand the relationship of hyperinsulinemia, a result of obesity, insulin resistance and increased IR signaling on the progression of breast cancer. Understanding these relationships could explain the different patterns of disease seen in different racial groups and help to identify patients who would benefit from targeted therapy. Our research attempts to address some of these gaps in the literature. We have 2 main aims: Aim 1: To examine whether the association between peripheral insulin resistance and breast cancer with a poor prognosis differs between black and white women. Aim 2: To demonstrate whether the tumor's insulin receptor and / or IGF-1 receptor signaling pathway is associated with poor prognostic features and whether activation of this pathway differs between black and white women. We will recruit 936 white women and 350 black women with a newly diagnosed breast cancer, to investigate the links between insulin resistance, breast cancer aggression, and race. Measures of insulin resistance, the metabolic syndrome and obesity will be collected to investigate whether insulin is a key mechanistic link in the association between obesity and breast cancer aggressivity, and how race affects this association. Blood samples for insulin resistance and anthropometric measures will be taken during the pre-operative evaluation of women with a new primary breast cancer. Samples of breast cancer tissue removed during primary surgical resection will be examined using immunohistochemistry to assess the role of insulin, insulin-like disparities in breast cancer prognosis between racial groups. PUBLIC HEALTH RELEVANCE: The purpose of this study is to determine whether differences in insulin resistance can explain in part the disparities in breast cancer survival between Black and White women. Insulin resistance is an important component of obesity, the metabolic syndrome and early stage type 2 diabetes, conditions associated with more aggressive breast cancer subtypes and increased mortality.